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One-pot synthesis of heterodimeric agonists that activate the canonical Wnt signaling pathway.


ABSTRACT: Fragment antigen-binding domains (Fabs) from anti-Frizzled and anti-LRP6 monoclonal antibodies were conjugated using SpyTag-SpyCatcher chemistry via a one-pot reaction. The resulting synthetic heterodimeric agonist outperformed the natural ligand, Wnt-3a, in activating canonical Wnt signaling in mammalian cells. This approach should be broadly applicable to activate receptor-mediated cellular signaling.

SUBMITTER: Mukherjee A 

PROVIDER: S-EPMC7179975 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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One-pot synthesis of heterodimeric agonists that activate the canonical Wnt signaling pathway.

Mukherjee Abhirup A   Stathos Mark E ME   Varner Chad C   Arsiwala Ammar A   Frey Steven S   Hu Yuge Y   Smalley David M DM   Schaffer David V DV   Kane Ravi S RS  

Chemical communications (Cambridge, England) 20200301 25


Fragment antigen-binding domains (Fabs) from anti-Frizzled and anti-LRP6 monoclonal antibodies were conjugated using SpyTag-SpyCatcher chemistry via a one-pot reaction. The resulting synthetic heterodimeric agonist outperformed the natural ligand, Wnt-3a, in activating canonical Wnt signaling in mammalian cells. This approach should be broadly applicable to activate receptor-mediated cellular signaling. ...[more]

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